The role of the newly discovered phosphoenolpyruvate carboxykinase ferroactivator in the regulation of gluconeogenesis in diabetic animals will be investigated. The catalytically active, as well as the total ferroactivator protein will be assayed with two techniques - by activation of purified P-enolpyruvate carboxykinase and by a specific radio-immunoassay. Efforts will be made to stabilize the catalytically active form and when this is achieved, the total ferroactivator protein and the catalytically active form will be assayed in the tissues from rats made diabetic with alloxan, and with streptozotocin. Similar assays will be conducted on tissues from genetically diabetic mice (db/db) at various times in their life cycle. Our goal is to determine what factors are responsible for the high rate of gluconeogenesis in diabetes and especially to learn if the ferroactivator protein plays a crucial role in making these high rates possible.